Microgravity produces three fundamental changes in human subjects: (a) a cephalad fluid shift; (b) altered proprioceptive, visual and vestibular sensory input; and (c) an unloaded musculoskeletal system. These perturbations produce complex and interdependent alterations which ultimately allow adaptation to microgravity. We suggest that the effect of these multiple, seemingly disparate influences on the autonomic nervous system produces the altered sympathetic activity suggested by recent studies in space. The overall goal of this proposal is to test the hypothesis that microgravity markedly alters sympathetic nervous system activity, and to define more precisely the consequences of microgravity on autonomic mechanisms of cardiovascular regulation, including sympathetic outflow, neural norepinephrine release and clearance, and postsynaptic receptor sensitivity. The study is ongoing.